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Thesystemfunction in the adult animal-is another prime example of such complex,coordinated cytoskeletalaction. For a cell to crawl, it must generateand maintain anouerall structural polarity, which is influenced by external cues.In addition, the cellmust coordinate protrusion at the leading edge(by assemblyof new actinfilaments),adhesion of the newly protruded part of the cell to the substratum,forcesgeneratedbymolecular motors to bring the cell bodyforward.Complexcells,such as neurons,require the coordinatedassemblyof microtubules,neurofilaments (neuronal intermediatefilaments), and actinftlaments, as well as theactions of dozensof highly specialized molecular motors that transport subcellularcomponentsto their appropriate destinations.PROBLEMSWhichstatementsare true? Explainwhy or why not.16-1 The role of ATP hydrolysisin actin polymerization issimilar to the role of GTP hydrolysis in tubulin polyrneriza_tion: both serve to weaken the bonds in the polymer andtherebypromote depolymerization.16-2 In most animal cells, minus end-directed micro_tubule motors delivertheir cargoto the periphery of the cell,whereasplus end-directedmicrotubule motors delivertheircargoto the interior ofthe cell.16-3 Motor neurons trigger action potentials in musclecell membranes that open voltage-sensitiveCa2*channelsin T-tubules, allowing extracellular CaZ*to enter the cytosol,bind to troponin C, and initiate rapid muscle contraction.1051PROBLEMSEND.OF-CHAPTER( B ) P O S I T I OONF K I N E S I N( A ) E X P E R I M E N TSAELT U PDiscussthe following problems.16-4 At 1.4 mg/ml pure tubulin, microtubules grow at arate of about 2 pm/min.
At this growth rate how many oBtubulin dimers (B nm in length) are added to the ends of amicrotubule each second?Euoa16*5 A solution of pure aB-tubulin dimers is thought tonucleate microtubules by forming a linear protofilamentabout sevendimers in length.At that point, the probabilitiesthat the next ap-dimer will bind laterallyor to the end of theprotofilament are about equal.The critical event for microtubule formation is thought to be the first lateralassociation(Figure Qf6-f). How does lateral associationpromote thesubsequentrapid formation of a microtubule?LATERALASSOCIATIONL I N E A RG R O W T Hoodo.cdo-,IIJe aod"tJeJe.t..ddd'lj,t'loofodddddddd.t.s,lJ,fby purecrB-tubulinnucleationFigureQ16-1Modelfor microtubuled i m e r(sP r o b l e1m6 5 ) .16-6 How does a centrosome"know" when it has foundthe center of the cell?16-7 The concentration of actin in cells is 50-100 timesgreater than the critical concentration observed for purepreventstheactin in a test tube.
How is this possible?'v\rhatactin subunits in cells from polymerizing into filaments?\A4ryis it advantageousto the cell to maintain such a largepool of actin subunits?16*8 The movements of single motor-protein moleculescan be analyzeddirectly.Using polarizedlaserlight, it is possible to create interferencepatterns that exert a centrallydirected force, ranging from zero aI the center to a fewpiconewtonsat the periphery (about 200 nm from the center). Individual molecules that enter the interferencepattern are rapidly pushed to the center,allowing them to becapturedand moved at the experimenter'sdiscretion.Using such "optical tweezers,"single kinesin moleculescan be positioned on a microtubule that is fixed to a coverslip.
Although a single kinesin molecule cannot be seenoptically,it can be taggedwith a silicabead and trackedindirectly by following the bead (Figure Qf 6-2,{). In the absenceof ATB the kinesin molecule remains at the center of theinterferencepattern, but with AIP it movestoward the plusend of the microtubule.As kinesin moves along the microtubule, it encountersthe force of the interferencepattern,which simulates the load kinesin carries during its actualfunction in the cell. Moreover,the pressureagainstthe silicabead countersthe effectsof Brownian (thermal)motion, sothat the position of the bead more accuratelyreflects theposition of the kinesin molecule on the microtubule.Tracesof the movements of a kinesin molecule along ain FigureQ16-28.microtubule are sho'nr,.nFqo208.,.1 o".onlu(Problentalonga microtubuleof kinesinFigureQ16-2Movementlinkedto a silicabead,setupwithkinesin16 s).(A)Experimental(asvisualizedby(B)Positionof kinesinmovingalonga microtubule.pattern,asaofinterferencecenterrelativetobead)ofsilicaDositionThejaggedalonqthemicrotubule'of timeof movementfunctionmotionof thebead'fromBrowniannatureof thetraceresultsomicrotubulemicrotubulezA.
As shown in Figure Ql6-2B, all movement of kinesin isin one direction (toward the plus end of the microtubule).\A4ratsuppliesthe free energyneededto ensurea unidirectional movement along the microtubule?B. \Altratis the averagerate of movement of kinesin alongthe microtubule?c. \A/hatis the length of each step that a kinesin takes as itmovesalong a microtubule?D. From other studies it is knor,rmthat kinesin has twoglobular domains that each can bind to B-tubulin, and thatkinesin moves along a single protofilament in a microtubule. In each protofilament the B-tubulin subunit repeatsat B-nm intervals.
Given the step length and the intervalbetween B-tubulin subunits,how do you supposea kinesinmoleculemovesalong a microtubule?E. Is there anything in the data in FigureQl6-28 that tellsyou how many AIP molecules are hydrolyzed per step?16-9 How is the unidirectional motion of a lamellipodiummaintained?16* 10 Detailedmeasurementsof sarcomerelength and tension during isometric contraction in striated muscle provided crucial early support for the sliding filament model ofmuscle contraction. Based on your understanding of thesliding filament model and the structure of a sarcomere,proposea molecular explanationfor the relationshipof tension to sarcomerelength in the portions of Figure Qf 6-3marked L II, III, and IV (In this muscle, the length of themyosin filament is 1.6pm and the lengths of the actin thinfilaments that project from the Z discsare 1.0pm.)FigureQl6-3 Tensionasafunction of sarcomerelengthduringisometriccontraction(Problem16-10).ElEi 100oE'b-50caz)q023sarcomerelength (Pm)1052Chapter16:TheCytoskeletonREFERENCESGeneralBrayD (2001)CellMovements:FromMoleculesto Motility,2nd edNewYork:GarlandScienceHoward.J(2001)Mechanicsof Motorproternsandthe CytoskeletonS u n d e r l a nMdA, :S i n a u e rThe Self-Assemblyand Dynamic Structure of CytoskeletalFilamentsDogteromM & YurkeB (1997)Measurementof the force-velocityrelationfor growingmicrotubuiesScience218856 860GarnerEC,CampbellCS& MullinsRD(2004)Dynamicinstabilityin aDNA-segregatingprokaryoticactinhomologScience306.10211O)5HelfandBT,ChangL & GoidmanRD(2003)Thedynamicand motilepropertiesof intermediatefilamentsAnnuRevCellDevBiol19.445,467HillTL& KirschnerMW (1982)Bioenergeticsand kineticsof microtubuleand actinfilamentassembly-disassemblylntRevCytol7B:1 125HotaniH & HorioT ('l9BB)Dynamicsof microtubulesvisualizedbydarkfieldmicroscopy:treadmillinganddynamicinstabilityCellMotilCytoskeleton10:229-236JonesLJ,Carballido-LopezR& ErringtonJ (2001)Conrrolofcellshapein bacteria:helical,actinlikefilamentsin BacillussubtilisCell104913-922LubyPhelpsK (2000)Cytoarchitectureand physicalpropertiesofcytoplasm:volume,viscosity,diffusion,intracellularsurfacearea/ntRevCytol192189-221MitchisonT & KirschnerM (1984)Dynamicinstabilityof microtubulegrowth A/rture312:237242MitchisonI I (1995)Evolutionof a dynamiccytoskeletonphilosTransRSocLondBBiol Sci349:299-304MukherjeeA & LutkenhausJ (1994)Guaninenucleotideoepenoentassemblyof FtsZintofilamentsJ Bacteriol116:27542/58OosawaF & AsakuraS (1975)Thermodynamicsof the polymerizationofpress,pp 41 55,pp 9O_1OBproteinNewYork:AcademicPaulingL (1953)Aggregationof GlobularproteinsDiscussFaradaySoc13.170-176RodionovVl & BorsyGG(,1997)Microtubuletreadmillingln vlvoS c i e n c2e/ 5 .
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rardeq3 t5g t1055OVERVIEWOFTHECELLCYCLEcytokinesismitosistransitionmetaphase-to-anaphaseINTERPHASEDNAreplicchromosomes are packaged into separate nuclei at telophase.
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